Zentrum fur Kinder und Jugendmedizin

Wuppertal, Germany

Zentrum fur Kinder und Jugendmedizin

Wuppertal, Germany
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Bierhals T.,Universitatsklinikum Hamburg Eppendorf | Korenke G.C.,Zentrum fur Kinder und Jugendmedizin | Uyanik G.,Universitatsklinikum Hamburg Eppendorf | Kutsche K.,Universitatsklinikum Hamburg Eppendorf
European Journal of Medical Genetics | Year: 2013

Pontocerebellar hypoplasias (PCH) represent a heterogeneous group of autosomal recessive neurodegenerative disorders characterized by hypoplasia of the cerebellum and pons, variable cerebral involvement, microcephaly, severe delay in cognitive and motor development, and seizures. Seven different subtypes have been reported (PCH1-7) and mutations in three genes, TSEN2, TSEN34 and TSEN54 encoding three of four subunits of the tRNA splicing endonuclease complex have been found to underlie PCH2, PCH4 and PCH5. PCH2 is characterized by cerebellar hypoplasia affecting the hemispheres more severely than the vermis, progressive cerebral atrophy and microcephaly, dyskinesia, seizures, and death in early childhood. We describe a male patient with progressive microcephaly, severe hypotonia, and myoclonic-tonic seizures. Brain MRI confirmed microcephaly with simplified cortical gyration and revealed hypoplasia of the brainstem, cerebellum and cerebellar vermis. Sequencing of the TSEN2 gene detected the novel missense mutation c.934G>A (p.G312R) on one allele and the first nonsense mutation c.691C>T (p.Q231*) on the second allele. Although the cytosine-to-thymine transition results in introduction of a premature stop codon in the majority of annotated TSEN2 transcript variants, it could represent a splice site mutation (c.517-3C>T) in variant 4. However, by RT-PCR analysis we did not identify mRNAs representing TSEN2 transcript form 4 in leukocyte-derived RNA of the patient and healthy individuals. The clinical phenotype of the patient is comparable with PCH2. However, we noticed decreased cerebral volume with increased extra-axial cerebrospinal fluid spaces and wide-open Sylvian fissures indicating cerebral immaturity that might be associated with the TSEN2 null allele. We conclude that the severity of pontocerebellar hypoplasia in the patient fits PCH2, while the large involvement of the cerebrum better corresponds to PCH4 demonstrating the phenotypic spectrum of PCH2 and 4. To establish a possible genotype-phenotype correlation, more individuals with biallelic TSEN2 mutations need to be investigated. © 2013 Elsevier Masson SAS.


Riffelmann M.,Institute For Hygiene Und Labormedizin | Thiel K.,Zentrum fur Kinder und Jugendmedizin | Schmetz J.,Institute For Hygiene Und Labormedizin | Wirsing Von Koenig C.H.,Institute For Hygiene Und Labormedizin
Journal of Clinical Microbiology | Year: 2010

Measuring antibodies to Bordetella pertussis antigens is mostly done by enzyme-linked immunosorbent assays (ELISAs). We compared the performance of ELISA kits that were commercially available in Germany. Eleven measured IgG antibodies, and nine measured IgA antibodies. An in-house ELISA with purified antigens served as a reference method. Samples included two WHO reference preparations, the former Food and Drug Administration (FDA)/Center for Biologics Evaluation and Research (CBER) reference preparations, serum samples from patients with clinically suspected pertussis, and serum samples from patients having received a combined tetanus, diphtheria, and pertussis (Tdap) vaccination. Kits using pertussis toxin (PT) as an antigen showed linearity compared to the WHO Reference preparation (r2 between 0.82 and 0.99), and these kits could quantify antibodies according to the reference preparation. ELISA kits using mixed antigens showed no linear correlation to the reference preparations. Patient results were compared to results of in-house ELISAs using a dual cutoff of either ≥100 IU/ml anti-PT IgG or ≥40 IU/ml anti-PT IgG together with ≥12 IU/ml anti-PT IgA. The sensitivities of kits measuring IgG antibodies ranged between 0.84 and 1.00. The specificities of kits using PT as an antigen were between 0.81 and 0.93. The specificities of kits using mixed antigens were between 0.51 and 0.59 and were thus not acceptable. The sensitivities of kits measuring IgA antibodies ranged between 0.53 and 0.73, and the specificities were between 0.67 and 0.94, indicating that IgA antibodies may be of limited diagnostic value. Our data suggest that ELISAs should use purified PT as an antigen and be standardized to the 1st International Reference preparation. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Weidenfeld A.,Wagener Stiftung fur Sozialpadiatrie | Borusiak P.,Zentrum fur Kinder und Jugendmedizin
Child's Nervous System | Year: 2011

Purpose: There are some reports of so-called Alice-in-Wonderland syndrome mostly concerning differential diagnosis, association with a variety of infectious diseases and even some case reports on functional imaging. Long-term data are rare. Methods: Nine boys aged 6 to 11 years that had been diagnosed with Alice-in-Wonderland syndrome between 2003 and 2008 were contacted for a long-term follow-up study in summer, 2009, with a mean follow-up of 4.6 years. Results: At the time of the follow-up study, all children were in good general and mental health. Symptoms of Alice-in-Wonderland syndrome had ceased within weeks or months. In two patients, episodes of metamorphopsia returned after a symptom-free latency of 3 years and 1 year, respectively. Five children had a family history of migraine or epilepsy. In one case, the father was reported to have experienced similar symptoms when he was a child. Conclusion: Our follow-up study shows that Alice-in-Wonderland is most likely a benign, self-terminating childhood condition, although occasional recurrences of symptoms are possible. © Springer-Verlag 2011.


Ozyurt J.,Carl von Ossietzky University | Lorenzen A.,Carl von Ossietzky University | Lorenzen A.,University of Kiel | Gebhardt U.,Zentrum fur Kinder und Jugendmedizin | And 3 more authors.
Neurobiology of Learning and Memory | Year: 2014

Albeit histologically low grade (WHO Io) brain tumors, craniopharyngiomas and/or their surgical removal frequently affect the hypothalamus, amongst other brain regions at risk. Due to rich hypothalamic connections with prefrontal and limbic regions, hypothalamic injury may adversely affect neural substrates of emotion processing and higher cognitive control, including memory and executive functions. The current study is the first to investigate the consequences of hypothalamic involvement on neural substrates of emotional and cognitive functioning. Ten patients with childhood craniopharyngioma and known hypothalamic involvement and fifteen age- and intelligence matched control subjects (median age: 17.8 and 17.3 yrs.) were studied with functional magnetic resonance imaging and an emotional face recognition task. During encoding, participants were asked to classify neutral and emotional faces. In a subsequent recognition phase, participants had to recognize these old faces within a set of new faces.Behavioral performance was comparable between patients and controls. Neural activity revealed, however, differential recruitment of fronto-limbic brain regions during recognition. Patients exhibited an abnormal pattern of task-induced activation and deactivation in the anterior and posterior rostral medial prefrontal cortex and a higher functional coupling between anterior rostral medial prefrontal cortex and the thalamus. Additionally, we found a higher reactivity in the patients' amygdala to emotional relative to neutral faces when compared to healthy controls.Our data provide first evidence that hypothalamic damage impacts neural correlates of memory retrieval in medial prefrontal cortex, indicating a less efficient use of an area involved in executive control processes. We propose that the deactivation failure in the patients' anterior rostral medial prefrontal cortex is related to an increased coupling with the thalamus and reflects a reduced efficiency to flexibly adapt to task demands. © 2014 Elsevier Inc.


Jenke A.C.,Zentrum fur Kinder und Jugendmedizin
Padiatrische Praxis | Year: 2013

Bell palsy is mainly a diagnosis of exclusion, but certain features in history, physical examination and laboratory parameters allow distinguishing it from facial paralysis due to other conditions. The most important differential diagnosis in children is neuroborreliosis. Cerebral imaging is usually not indicated except for patients with persistent paralysis and/or symptoms suggestive for other systemic disorders. In adults apart from physiotherapy and corneal protection corticosteroids given within 10 days of onset have been shown to improve the outcome. In children, there are no clinical studies assessing the benefits of systemic corticosteroids. Therefore, since the rate of spontaneous remission of BELL palsy in children is almost 98% systemic corticosteroids cannot be recommended in pediatric patients.


Hoger P.H.,Zentrum fur Kinder und Jugendmedizin
Monatsschrift fur Kinderheilkunde | Year: 2015

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in children. In 60–80 % of all cases it manifests during the first year of life. AD pathogenesis is characterized by an interplay between genetic disposition (barrier defect, excessive cutaneous inflammation) and an increased susceptibility to reacting to triggering factors (infections, allergens, “stress”). Therapy: In every stage of the disease, barrier therapy is crucial. Restoration of the defective barrier prevents transepidermal water loss as well as intrusion of allergens and pathogens from outside that promote cutaneous inflammation. Topical barrier therapy should be adapted to the disease stage, the location of the eczema, the season, and the age of the child. Proactive topical anti-inflammatory therapy is based on “modern” topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Among a wide selection of TCS, prednicarbate and methylprednisolone are preferred owing to their favorable safety/efficacy profile. According to recently published studies, the same applies to TCI, which are ideally suited for long-term therapy in order to prevent relapses. Conclusion: A total of 90–95% of cases can be effectively controlled by topical therapy tailored to the disease state and patient age. Therapy aims at disease control and prevention of recurrences. © 2015, Springer-Verlag Berlin Heidelberg.


Borusiak P.,Zentrum fur Kinder und Jugendmedizin | Zilbauer M.,Zentrum fur Kinder und Jugendmedizin | Jenke A.C.W.,Zentrum fur Kinder und Jugendmedizin
Epilepsia | Year: 2010

Purpose: Data on epileptiform electroencephalography (EEG) discharges in healthy children are limited, with published studies dating back more than 20 years. Moreover, analyses have been performed exclusively using paper-recorded EEG, and reported prevalences differ significantly. With recent reports using these data as reference suggesting an increased prevalence of epileptiform EEG discharges in children with behavioral disturbances, acquisition of exact prevalence data has become even more critical. The aim of our study was to analyze the frequency of epileptiform EEG discharges in healthy children using digitally recorded EEG (DEEG) and to compare these data to those of previously published studies. Methods: Prospective analysis of DEEG was performed in 382 healthy children (226 male, 156 female) ages 6-13 years admitted to our hospital for minor head trauma. Recording was carried out for a minimum of 20 min including hyperventilation and photic stimulation. Analysis was carried out by two board-certified clinical neurophysiologists. Results: Epileptiform EEG discharges were detected in 25 of 382 children (11 of 226 male, 14 of 156 female) corresponding to an overall prevalence of 6.5%. Of these 25 children, 4 had either generalized or bifrontal spikes, 12 showed constant localized focal discharges, and 9 showed multifocal discharges. Compared to previous studies using non-DEEG recording, the prevalence of epileptiform EEG discharges in our population was significantly higher. No significant difference was found when comparing our data to prevalences recently reported in children with behavioral disturbances using DEEG. Conclusions: Our study further highlights the urgent need to reevaluate the prevalence of epileptiform EEG discharges in healthy children using DEEG recordings in a large cohort. ©2009 International League Against Epilepsy.


Muller H.L.,Zentrum fur Kinder und Jugendmedizin
Nature Reviews Endocrinology | Year: 2010

Craniopharyngiomas have an overall incidence of 0.5-2.0 new cases per million of the population per year, and ∼30-50% of all cases represent childhood craniopharyngioma. These partly cystic embryogenic malformations of the sellar region are presumably derived from Rathke cleft epithelium. Many of the typical manifestations at primary diagnosis are nonspecific and include headache, visual impairment, polyuria and/or polydypsia, growth retardation and weight gain. Total resection is the treatment of choice in patients with favorable tumor localization, with the intention to maintain hypothalamic-pituitary and optical nerve functions. When the tumor localization is unfavorable, a limited resection followed by local irradiation is recommended. The overall survival rates are high (91-98%). High recurrence rates after complete resection and high progression rates after incomplete resection have been observed, although the risk of recurrence or progression is less after complete resection than partial resection. Irradiation of the tumor is protective and the appropriate time point of irradiation after incomplete resection is currently under investigation in a randomized trial. Long-term sequelae substantially reduce the quality of life of ∼50% of long-term survivors, notably extreme obesity owing to hypothalamic involvement. © 2010 Macmillan Publishers Limited. All rights reserved.


Muller H.L.,Zentrum fur Kinder und Jugendmedizin
Expert Review of Neurotherapeutics | Year: 2010

Craniopharyngiomas are embryogenic malformations of the sellar region of low histological malignancy, thought to be derived from Rathke's pouch epithelium. With an overall incidence of 0.5-2.0 new cases per million of the population per year, 30-50% of all cases occur in childhood. Overall survival rates are high. However, quality of survival is substantially reduced in many survivors, owing to long-term sequelae, such as extreme obesity caused by hypothalamic tumor involvement, which occurs in up to 40% of all cases. The treatment of craniopharyngioma remains controversial. Radical surgical strategies are associated with poor outcome in craniopharyngioma with hypothalamic involvement. © 2010 Expert Reviews Ltd.


Jenke A.C.,Zentrum fur Kinder und Jugendmedizin
Chirurgische Praxis | Year: 2014

Bell palsy is mainly a diagnosis of exclusion, but certain features in history, physical examination and laboratory parameters allow distinguishing it from facial paralysis due to other conditions. The most important differential diagnosis in children is neuroborreliosis. Cerebral imaging is usually not indicated except for patients with persistent paralysis and/or symptoms suggestive for other systemic disorders. In adults apart from physiotherapy and corneal protection corticosteroids given within 10 days of onset have been shown to improve the outcome. In children, there are no clinical studies assessing the benefits of systemic corticosteroids. Therefore, since the rate of spontaneous remission of BELL palsy in children is almost 98% systemic corticosteroids cannot be recommended in pediatric patients.

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